We request funds for a Leica TCS SPII confocal microscope to replace our older failing model and upgrade our facility to maintain cutting edge technologies. As configured this system maintains the excellent light transmission, spectral separation and tunability we are familiar with on our current Leica SP2 AOBS system and adds tandem scanning for improved live cell imaging and hybrid detectors for greater sensitivity, better contrast and extended dynamic range in our multiparameter studies. The system will be installed in a well- established shared Imaging Core Facility in the Department of Genetics at Case Western Reserve University. Our facility offers access to numerous outside researchers as well as the well-funded NIH investigators named within. Our aim is to provide state-of-the-art instrumentation and technical expertise to aid our investigators in their basic, clinical, and translational research. The principle investigators who will initially benefit from this system wor on a broad array of organisms and health-related issues, including the factors affecting migration, differentiation, and development of primordial germ cells (mutations in which lead to testicular cancer), the role of Ca2+ transients in sudden cardiac death (germane to cell therapies to restore cardiac function in heart disease), defining host-pathogen molecular interactions associated with fungal infections (with the goal of developing better strategies to alleviate resistance), and examining transport and neurotoxicity in Prion Diseases (with the goal of determining pathogenesis.). Three projects involve sensory hair cells and their relationship to either vision or hearing loss (one examines membrane protein trafficking in rod photoreceptor cells, deficiencies in which lead to blindness, one focuses on the structure of rhodopsin and its role in retinal degeneration, and one examines mutations in sensory hair cells in the inner ear which have been linked to hearing loss in Usher Syndrome). One project aims to develop diagnostic detection agents for disease (tumor- targeted nanobubbles) with the eventual goal of establishing target-based therapies. All of these projects use methods of multiparameter mapping strategies in living and fixed cells and tissues and critically need the capabilities of th requested SP5 confocal for their NIH-funded projects to move forward.